scholarly journals Down-regulation of β3-adrenergic receptor expression in rat adipose tissue during the fasted/fed transition: evidence for a role of insulin

1997 ◽  
Vol 323 (2) ◽  
pp. 359-364 ◽  
Author(s):  
Khadija El HADRI ◽  
Christine CHARON ◽  
Jacques PAIRAULT ◽  
Sylvie HAUGUEL-DE MOUZON ◽  
Annie QUIGNARD-BOULANGÉ ◽  
...  

The β3-adrenergic receptor (β3-AR) exerts a central role in the transduction of catecholamine effects in white and brown adipose tissue (WAT and BAT). A recent report has documented that insulin strongly down-regulates β3-AR expression and catecholamine responsiveness in 3T3-F442A adipocytes [Fève, El Hadri, Quignard-Boulangé and Pairault (1994) Proc. Natl. Acad. Sci. U.S.A. 91, 5677–5681]. In the present report we show that the rise in plasma insulin levels elicited by the fasted/fed transition is associated with a reduction in β3-AR mRNA levels and β-adrenergic responsiveness in WAT and BAT. β3-AR transcripts are also decreased in adipose tissue from animals subjected for 6 h to euglycaemic hyperinsulinaemic glucose clamps. Moreover, insulin acts directly on cultured rat white and brown adipocytes to decrease β3-AR gene expression and adenylate cyclase activity in response to β3-AR-selective agonists. These results suggest that there is a close relationship between food intake, plasma insulin levels and β3-AR expression.

1991 ◽  
Vol 277 (3) ◽  
pp. 625-629 ◽  
Author(s):  
J P Revelli ◽  
R Pescini ◽  
P Muzzin ◽  
J Seydoux ◽  
M G Fitzgerald ◽  
...  

The aim of the present work was to study the effect of hypothyroidism on the expression of the beta-adrenergic receptor (beta-AR) in interscapular brown adipose tissue and heart. The total density of plasma membrane beta-AR per tissue is decreased by 44% in hypothyroid rat interscapular brown adipose tissue and by 55% in hypothyroid rat heart compared with euthyroid controls. The effects of hypothyroidism on the density of both beta 1- and beta 2-AR subtypes were also determined in competition displacement experiments. The densities of beta 1- and beta 2-AR per tissue are decreased by 50% and 48% respectively in interscapular brown adipose tissue and by 52% and 54% in the heart. Northern blot analysis of poly(A)+ RNA from hypothyroid rat interscapular brown adipose tissue demonstrated that the levels of beta 1- and beta 2-AR mRNA per tissue are decreased by 73% and 58% respectively, whereas in hypothyroid heart, only the beta 1-AR mRNA is decreased, by 43%. The effect of hypothyroidism on the beta 1-AR mRNA is significantly more marked in the interscapular brown adipose tissue than in the heart. These results indicate that beta-AR mRNA levels are differentially regulated in rat interscapular brown adipose tissue and heart, and suggest that the decrease in beta-AR number in interscapular brown adipose tissue and heart of hypothyroid animals may in part be explained by a decreased steady-state level of beta-AR mRNA.


1997 ◽  
Vol 322 (1) ◽  
pp. 145-150 ◽  
Author(s):  
John N. FAIN ◽  
Elizabeth C. CORONEL ◽  
Michael J. BEAUCHAMP ◽  
Suleiman W. BAHOUTH

The level of leptin [the obese (ob) gene product] mRNA is markedly elevated in hypothyroid male rats. The administration of tri-iodothyronine (T3) to hypothyroid rats resulted in a 40% decrease in leptin mRNA at 8 h. This decrease in leptin mRNA was associated with a parallel decline in circulating leptin levels of about 50% at 24 h. Conversely, β3-adrenergic receptor mRNA levels were markedly decreased in epididymal adipose tissue from hypothyroid rats. T3 administration resulted in a 147% increase at 12 h in β3-adrenergic receptor mRNA. There was a corresponding increase due to T3 in the lipolytic response to the specific β3-adrenergic agonist CL 316,243 that paralleled the increase in β3-adrenergic receptor mRNA. T3-mediated changes in leptin and β3-adrenergic receptor mRNAs were blocked by cycloheximide, suggesting the involvement of short-lived proteins in these effects. The present results indicate that T3 has opposite effects to those of insulin on the white adipose tissue of rats with respect to leptin mRNA expression.


2008 ◽  
Vol 197 (1) ◽  
pp. 55-64 ◽  
Author(s):  
B Gálvez-Prieto ◽  
J Bolbrinker ◽  
P Stucchi ◽  
A I de las Heras ◽  
B Merino ◽  
...  

Recent studies have demonstrated that the rat adipose tissue expresses some of the components necessary for the production of angiotensin II (Ang II) and the receptors mediating its actions. The aim of this work is to characterize the expression of the renin–angiotensin system (RAS) components in perivascular adipose tissue and to assess differences in the expression pattern depending on the vascular bed and type of adipose tissue. We analyzed Ang I and Ang II levels as well as mRNA levels of RAS components by a quantitative RT-PCR method in periaortic (PAT) and mesenteric adipose tissue (MAT) of 3-month-old male Wistar–Kyoto rats. PAT was identified as brown adipose tissue expressing uncoupling protein-1 (UCP-1). It had smaller adipocytes than those from MAT, which was identified as white adipose tissue. All RAS components, except renin, were detected in both PAT and MAT. Levels of expression of angiotensinogen, Ang-converting enzyme (ACE), and ACE2 were similar between PAT and MAT. Renin receptor expression was five times higher, whereas expression of chymase, AT1a, and AT2 receptors were significantly lower in PAT compared with MAT respectively. In addition, three isoforms of the AT1a receptor were found in perivascular adipose tissue. The AT1b receptor was found at very a low expression level. Ang II levels were higher in MAT with no differences between tissues in Ang I. The results show that the RAS is differentially expressed in white and brown perivascular adipose tissues implicating a different role for the system depending on the vascular bed and the type of adipose tissue.


1987 ◽  
Vol 252 (3) ◽  
pp. R471-R478 ◽  
Author(s):  
B. E. Levin ◽  
J. Triscari ◽  
S. Hogan ◽  
A. C. Sullivan

After 15 wk on a moderately high-calorie high-fat (CM) diet, 43% of 40 3-mo-old male Sprague-Dawley rats developed diet-induced obesity (DIO) (29% more weight gain), whereas 57% of diet-resistant (DR) rats gained no more weight than 20 chow-fed controls. When switched to chow for another 7 wk, DR rats ate 13% less, gained 55% less weight, and had 49% lower food efficiency, whereas DIO rats ate 4% less but had comparable weight gain and efficiency to controls. DIO rats had 29% more carcass lipid (percent of carcass weight). DIO rat retroperitoneal white adipose pads had 65% more cells that were the same size as those in chow-fed pads; DR rat cells were similar to controls. Both DR and DIO rats increased norepinephrine turnover in their interscapular brown adipose pads by greater than 90%. DIO rats also had 40% lower pancreatic turnover; their plasma insulin levels were 327% of controls after 15 wk on the CM diet and 188% after 7 wk on chow. DR levels were the same as controls at both times. Therefore, regulation of caloric intake, pancreatic sympathetic tone, and plasma insulin levels were three important differences between rats that resisted and those that developed DIO on high-energy diets.


Diabetes Care ◽  
1995 ◽  
Vol 18 (3) ◽  
pp. 292-299 ◽  
Author(s):  
A. Tchernof ◽  
J.-P. Despres ◽  
A. Dupont ◽  
A. Belanger ◽  
A. Nadeau ◽  
...  

1998 ◽  
Vol 275 (2) ◽  
pp. E259-E264 ◽  
Author(s):  
Philip J. Scarpace ◽  
Michael Matheny

We previously demonstrated that leptin increases uncoupling protein 1 (UCP1) and lipoprotein lipase (LPL) gene expression in brown adipose tissue (BAT) of rats. To determine whether the induction of these transcripts is dependent on sympathetic innervation of BAT, we unilaterally surgically denervated interscapular BAT in both pair-fed and leptin (0.9 mg/day by infusion)-treated rats. In pair-fed rats, the level of UCP1 mRNA in the denervated BAT pad was 30–47% less than in the innervated pad. In the intact BAT pad, leptin administration increased UCP1 mRNA levels by nearly 2.5-fold compared with pair-fed rats. In contrast, in the denervated BAT pad, there was no increase in UCP1 gene expression. When LPL mRNA was examined in pair-fed rats, there was no difference between innervated and denervated BAT pads. With leptin administration, LPL gene expression increased by 75% in both the innervated and denervated BAT pads. β3-Adrenergic receptor mRNA was unaffected by either denervation or leptin, whereas uncoupling protein 2 mRNA levels were increased in epididymal white adipose tissue (WAT) but not in perirenal WAT. CGP-12177, a specific β3-adrenergic receptor agonist, induced nearly a fourfold increase in UCP1 and a twofold increase in LPL gene expression in both the innervated and denervated BAT pads. These data indicate that the leptin induction of UCP1 gene expression in BAT is dependent on sympathetic innervation but that the leptin induction of LPL gene expression is not.


1992 ◽  
Vol 288 (2) ◽  
pp. 675-679 ◽  
Author(s):  
R Burcelin ◽  
M Eddouks ◽  
J Kande ◽  
R Assan ◽  
J Girard

GLUT-2, glucokinase (GK) and phosphoenolpyruvate carboxykinase (PEPCK) mRNA expression was studied in the liver of chronically catheterized diabetic rats during the 3 days after an intravenous injection of 65 mg of streptozotocin (STZ)/kg. At 6 h after the STZ injection, portal plasma insulin levels were 270 +/- 32 mu-units/ml and blood glucose was 1.4 +/- 0.4 mmol/l, owing to pancreatic beta-cell destruction. GLUT-2 and PEPCK mRNA concentrations were rapidly and dramatically decreased (> 90%), whereas GK mRNA was increased. After 30 h, plasma insulin concentrations were lower than 5 mu-units/ml and blood glucose was > 20 mmol/l. GLUT-2 and PEPCK mRNA concentrations increased 2-fold and GK mRNA disappeared progressively. In order to assess the relative roles of hyperglycaemia and insulinopenia, blood glucose was clamped at 6.4 +/- 0.5 mmol/l from 18 to 72 h after STZ injection by phlorizin infusion (0.5-2 g/day per kg) or at 6.6 +/- 0.3 mmol/l from 18 to 48 h after STZ injection by insulin infusion (0.25 unit/min per kg). GLUT-2 mRNA concentrations were 50% lower in phlorizin-infused than in untreated diabetic rats. The low levels of GK mRNA and the high levels of PEPCK mRNA were unaffected by normalization of hyperglycaemia in phlorizin-infused diabetic rats. In insulin-infused rats (portal plasma insulin levels of 40 mu-units/ml) GLUT-2 mRNA levels were 25% of those in untreated diabetic rats, and they increased rapidly 6 h after insulin infusion was stopped. Liver GLUT-2 protein concentration showed similar changes in response to STZ injection and to phlorizin or insulin treatment, but after a delay of several hours. From this work we conclude that GLUT-2 gene expression is dramatically and rapidly (< 6 h) decreased by portal hyperinsulinaemia and increased by hyperglycaemia.


2011 ◽  
Vol 301 (6) ◽  
pp. E1081-E1091 ◽  
Author(s):  
Annette D. de Kloet ◽  
Eric G. Krause ◽  
Karen A. Scott ◽  
Michelle T. Foster ◽  
James P. Herman ◽  
...  

Considerable evidence implicates the renin-angiotensin system (RAS) in the regulation of energy balance. To evaluate the role of the RAS in the central nervous system regulation of energy balance, we used osmotic minipumps to chronically administer angiotensin II (Ang II; icv; 0.7 ng/min for 24 days) to adult male Long-Evans rats, resulting in reduced food intake, body weight gain, and adiposity. The decrease in body weight and adiposity occurred relative to both ad libitum- and pair-fed controls, implying that reduced food intake in and of itself does not underlie all of these effects. Consistent with this, rats administered Ang II had increased whole body heat production and oxygen consumption. Additionally, chronic icv Ang II increased uncoupling protein-1 and β3-adrenergic receptor expression in brown adipose tissue and β3-adrenergic receptor expression in white adipose tissue, which is suggestive of enhanced sympathetic activation and thermogenesis. Chronic icv Ang II also increased hypothalamic agouti-related peptide and decreased hypothalamic proopiomelanocortin expression, consistent with a state of energy deficit. Moreover, chronic icv Ang II increased the anorectic corticotrophin- and thyroid-releasing hormones within the hypothalamus. These results suggest that Ang II acts in the brain to promote negative energy balance and that contributing mechanisms include an alteration in the hypothalamic circuits regulating energy balance, a decrease in food intake, an increase in energy expenditure, and an increase in sympathetic activation of brown and white adipose tissue.


2005 ◽  
Vol 288 (1) ◽  
pp. E200-E207 ◽  
Author(s):  
S. Rodriguez-Cuenca ◽  
M. Monjo ◽  
A. M. Proenza ◽  
P. Roca

Sex hormones play an important role in adipose tissue metabolism by activating specific receptors that alter several steps of the lipolytic and lipogenic signal cascade in depot- and sex-dependent manners. However, studies focusing on steroid receptor status in adipose tissue are scarce. In the present study, we analyzed steroid content [testosterone (T), 17β-estradiol (17β-E2), and progesterone (P4)] and steroid receptor mRNA levels in different rat adipose tissue depots. As expected, T levels were higher in males than in females ( P = 0.031), whereas the reverse trend was observed for P4 ( P < 0.001). It is noteworthy that 17β-E2 adipose tissue levels were higher in inguinal than in the rest of adipose tissues for both sexes, where no sex differences in 17β-E2 tissue levels were noted ( P = 0.010 for retroperitoneal, P = 0.005 for gonadal, P = 0.018 for mesenteric). Regarding steroid receptor levels, androgen (AR) and estrogen receptor (ER)α and ERβ densities were more clearly dependent on adipose depot location than on sex, with visceral depots showing overall higher mRNA densities than their subcutaneous counterparts. Besides, expression of ERα predominated over ERβ expression, and progesterone receptor (PR-B form and PR-A+B form) mRNAs were identically expressed regardless of anatomic depot and sex. In vitro studies in 3T3-L1 cells showed that 17β-E2 increased ERα ( P = 0.001) and AR expression ( P = 0.001), indicating that estrogen can alter estrogenic and androgenic signaling in adipose tissue. The results highlighted in this study demonstrate important depot-dependent differences in the sensitivity of adipose tissues to sex hormones between visceral and subcutaneous depots that could be related to metabolic situations observed in response to sex hormones.


2015 ◽  
Vol 228 (1) ◽  
pp. 1-12 ◽  
Author(s):  
Hamza Amine ◽  
Yacir Benomar ◽  
Adil Haimeur ◽  
Hafida Messaouri ◽  
Nadia Meskini ◽  
...  

The beneficial effect of polyunsaturated omega-3 fatty acid (w-3 FA) consumption regarding cardiovascular diseases, insulin resistance and inflammation has been widely reported. Fish oil is considered as the main source of commercialized w-3 FAs, and other alternative sources have been reported such as linseed or microalgae. However, despite numerous reports, the underlying mechanisms of action of w-3 FAs on insulin resistance are still not clearly established, especially those from microalgae. Here, we report that Odontella aurita, a microalga rich in w-3 FAs eicosapentaenoic acid, prevents high fat diet-induced insulin resistance and inflammation in the liver of Wistar rats. Indeed, a high fat diet (HFD) increased plasma insulin levels associated with the impairment of insulin receptor signaling and the up-regulation of toll-like receptor 4 (TLR4) expressions. Importantly, Odontella aurita-enriched HFD (HFOA) reduces body weight and plasma insulin levels and maintains normal insulin receptor expression and responsiveness. Furthermore, HFOA decreased TLR4 expression, JNK/p38 phosphorylation and pro-inflammatory factors. In conclusion, we demonstrate for the first time, to our knowledge, that diet supplementation with whole Ondontella aurita overcomes HFD-induced insulin resistance through the inhibition of TLR4/JNK/p38 MAP kinase signaling pathways.


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